HUP0204418A2 - Nhe-1 inhibitor n-[(substituted five-membered di- or triaza diunsaturated ring)carbonyl] guanidine derivatives and use thereof - Google Patents

Nhe-1 inhibitor n-[(substituted five-membered di- or triaza diunsaturated ring)carbonyl] guanidine derivatives and use thereof

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Publication number
HUP0204418A2
HUP0204418A2 HU0204418A HUP0204418A HUP0204418A2 HU P0204418 A2 HUP0204418 A2 HU P0204418A2 HU 0204418 A HU0204418 A HU 0204418A HU P0204418 A HUP0204418 A HU P0204418A HU P0204418 A2 HUP0204418 A2 HU P0204418A2
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HU
Hungary
Prior art keywords
membered
substituted
unsaturated
alkyl
compounds
Prior art date
Application number
HU0204418A
Other languages
Hungarian (hu)
Inventor
Angel Guzman-Perez
Ernest S. Hamanaka
Christian J. Mularski
Roger B. Ruggeri
Ronald T. Wester
Original Assignee
Pfizer Products Inc.
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Filing date
Publication date
Application filed by Pfizer Products Inc. filed Critical Pfizer Products Inc.
Publication of HUP0204418A2 publication Critical patent/HUP0204418A2/en
Publication of HUP0204418A3 publication Critical patent/HUP0204418A3/en

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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D231/00Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/02Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
    • C07D231/10Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D231/12Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/425Thiazoles
    • A61K31/428Thiazoles condensed with carbocyclic rings
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00Drugs for disorders of the urinary system
    • A61P13/12Drugs for disorders of the urinary system of the kidneys
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00Drugs for skeletal disorders
    • A61P19/04Drugs for skeletal disorders for non-specific disorders of the connective tissue
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00Drugs for disorders of the metabolism
    • A61P3/08Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P41/00Drugs used in surgical methods, e.g. surgery adjuvants for preventing adhesion or for vitreum substitution
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • A61P9/06Antiarrhythmics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • A61P9/10Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • A61P9/12Antihypertensives
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D231/00Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/02Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
    • C07D231/10Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D231/14Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D233/00Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
    • C07D233/54Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
    • C07D233/56Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D249/00Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
    • C07D249/02Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
    • C07D249/041,2,3-Triazoles; Hydrogenated 1,2,3-triazoles
    • C07D249/061,2,3-Triazoles; Hydrogenated 1,2,3-triazoles with aryl radicals directly attached to ring atoms
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    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D249/00Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
    • C07D249/02Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
    • C07D249/081,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
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    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D401/00Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/04Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
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    • C07DHETEROCYCLIC COMPOUNDS
    • C07D403/00Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/04Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
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    • C07DHETEROCYCLIC COMPOUNDS
    • C07D405/00Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/04Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
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    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D413/00Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/04Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D417/00Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/04Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond

Abstract

A találmány tárgya (I) általános képletű vegyületek, előgyógyszereikvagy a vegyületek vagy előgyógyszereik gyógyászatilag elfogadható sói,a képletben Z jelentése szénatomon keresztül kapcsolódó 5-tagú, kétszomszédos nitrogénatomot tartalmazó kétszeresen telítetlen gyűrű,amely adott esetben az R1, R2 és R3 helyettesítők közül egymástólfüggetlenül választott legfeljebb három csoporttal helyettesített;vagy Z jelentése szénatomon keresztül kapcsolódó 5-tagú, háromnitrogénatomot és két telítetlen kötést tartalmazó gyűrű, amely adottesetben egymástól függetlenül az R4 és R5 helyettesítők közülválasztott legfeljebb két helyettesítővel helyettesített; ahol R1, R2,R3, R4 és R5 jelentése egymástól függetlenül hidrogénatom, hidroxi-alkil-, alkil-, alkil-tio-, cikloalkil-, cikloalkil-alkil-, alkoxi-,alkoxi-alkil-, mono-N- vagy di-N,N-karbamoil-, M vagy M-alkil-csoport,ahol a fenti alkilmolekula részek adott esetben 1-9 fluoratomottartalmaznak; továbbá az alkil- vagy cikloalkilcsoportok adott esetbenegymástól függetlenül helyettesítettek; ahol M jelentése részlegesentelített, teljesen telített vagy teljesen telítetlen 5-8 tagúheterogyűrű, vagy két kondenzált részlegesen telített, teljesentelített vagy teljesen telítetlen 3-6-tagú gyűrűből álló biciklusosheterogyűrű; továbbá M adott esetben legfeljebb három csoporttalhelyettesített. A találmány tárgyát képezi továbbá a fenti vegyületekalkalmazása nátrium-hidrogén csere 1 típusú (NHE-1) gátló hatásúgyógyászati készítmények előállítására, amelyek előnyösen isémiakezelésére alkalmasak. ÓThe subject of the invention is compounds of the general formula (I), their prodrugs or pharmaceutically acceptable salts of the compounds or their prodrugs, in the formula Z is a 5-membered doubly unsaturated ring containing two neighboring nitrogen atoms connected through a carbon atom, which is optionally chosen independently from among the substituents R1, R2 and R3 substituted by up to three groups; or Z is a 5-membered ring connected through a carbon atom, containing three nitrogen atoms and two unsaturated bonds, optionally substituted by up to two substituents selected from the R4 and R5 substituents; where R 1 , R 2 , R 3 , R 4 and R 5 are independently hydrogen, hydroxyalkyl, alkyl, alkylthio, cycloalkyl, cycloalkylalkyl, alkoxy, alkoxyalkyl, mono-N or di -N,N-carbamoyl, M or M-alkyl group, where the above alkyl molecular parts optionally contain 1-9 fluorine atoms; moreover, the alkyl or cycloalkyl groups are optionally substituted independently of each other; where M is a partially unsaturated, fully saturated or fully unsaturated 5-8 membered heteroring, or a bicyclic heteroring consisting of two fused partially saturated, fully saturated or fully unsaturated 3-6 membered rings; moreover, M may be substituted by up to three groups. The subject of the invention is also the use of the above compounds for the production of medicinal preparations with an inhibitory effect on sodium hydrogen exchange type 1 (NHE-1), which are advantageously suitable for the treatment of ischemia. HE

HU0204418A 1998-02-27 1999-02-05 Nhe-1 inhibitor n-[(substituted five-membered di- or triaza diunsaturated ring)carbonyl] guanidine derivatives and use thereof HUP0204418A3 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US7636298P 1998-02-27 1998-02-27
PCT/IB1999/000206 WO1999043663A1 (en) 1998-02-27 1999-02-05 N-[(substituted five-membered di- or triaza diunsaturated ring)carbonyl] guanidine derivatives for the treatment of ischemia

Publications (2)

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HUP0204418A2 true HUP0204418A2 (en) 2003-04-28
HUP0204418A3 HUP0204418A3 (en) 2003-10-28

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US (2) US6492401B1 (en)
EP (2) EP1056729B1 (en)
JP (2) JP2002504546A (en)
KR (4) KR100407903B1 (en)
CN (1) CN1289326A (en)
AP (1) AP9901478A0 (en)
AR (1) AR015526A1 (en)
AT (1) ATE286034T1 (en)
AU (1) AU739403B2 (en)
BG (1) BG104803A (en)
BR (1) BR9908332A (en)
CA (1) CA2321642A1 (en)
CO (1) CO4980897A1 (en)
DE (1) DE69922930T2 (en)
DK (1) DK1056729T3 (en)
DZ (1) DZ2729A1 (en)
EA (1) EA003603B1 (en)
ES (1) ES2237080T3 (en)
GT (1) GT199900022A (en)
HR (2) HRP20000550A2 (en)
HU (1) HUP0204418A3 (en)
ID (1) ID25505A (en)
IL (1) IL136588A0 (en)
IS (1) IS5548A (en)
NO (1) NO20004192L (en)
NZ (1) NZ504769A (en)
OA (1) OA11450A (en)
PA (1) PA8468401A1 (en)
PE (1) PE20000334A1 (en)
PL (1) PL342444A1 (en)
PT (1) PT1056729E (en)
SI (1) SI1056729T1 (en)
SK (1) SK12342000A3 (en)
TN (1) TNSN99028A1 (en)
TR (1) TR200002480T2 (en)
TW (1) TWI226329B (en)
WO (1) WO1999043663A1 (en)
YU (1) YU46200A (en)
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